Susceptibility of male wild type mouse strains to antipsychotic-induced weight gain

ABSTRACT In vitro screening using the cell-free prion protein conversion system indicated that certain rodents may be susceptible to chronic wasting disease (CWD). Therefore, CWD isolates from mule deer, white-tailed deer, and elk were inoculated intracerebrally into various rodent species to assess the rodents' susceptibility and to develop new rodent models of CWD. The species inoculated were Syrian golden, Djungarian, Chinese, Siberian, and Armenian hamsters, transgenic mice expressing the Syrian golden hamster prion protein, and RML Swiss and C57BL10 wild-type mice. The transgenic mice and the Syrian golden, Chinese, Siberian, and Armenian hamsters had limited susceptibility to certain of the CWD inocula, as evidenced by incomplete attack rates and long incubation periods. For serial passages of CWD isolates in Syrian golden hamsters, incubation periods rapidly stabilized, with isolates having either short (85 to 89 days) or long (408 to 544 days) mean incubation periods and distinct neuropathological patterns. In contrast, wild-type mouse strains and Djungarian hamsters were not susceptible to CWD. These results show that CWD can be transmitted and adapted to some species of rodents and suggest that the cervid-derived CWD inocula may have contained or diverged into at least two distinct transmissible spongiform encephalopathy strains.

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Comprehensive characterization of motor and coordination functions in three adolescent wild-type mouse strains

Scientific Reports ◽

10.1038/s41598-021-85858-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ahmed Eltokhi ◽

Barbara Kurpiers ◽

Claudia Pitzer

Keyword(s):

Developmental Stages ◽

Wild Type Mouse ◽

Neuropsychiatric Disorders ◽

Autism Spectrum ◽

Face Validity ◽

Mouse Strains ◽

Behavioral Tests ◽

Wild Type ◽

Behavioral Experiments ◽

Behavioral Studies

AbstractNeuropsychiatric disorders are often associated with motor and coordination abnormalities that have important implications on the etiology, pathophysiology, and management of these disorders. Although the onset of many neuropsychiatric disorders including autism spectrum disorder, schizophrenia, and attention-deficit hyperactivity disorder emerges mainly during infancy and adolescence, most of the behavioral studies in mice modeling neuropsychiatric phenotypes are performed in adult animals, possibly missing valuable phenotypic information related to the effect of synaptic maturation during development. Here, we examined which behavioral tests assessing both motor and coordination functions can be performed in mice at two different adolescent stages. As strain and sex affect mouse behavior, our experiments covered both male and female mice of three inbred wild-type strains, C57BL/6N, DBA/2, and FVB/N. Adolescent mice of both postnatal days (P)22–30 and P32–40 developmental stages were capable of mastering common motor and coordination tests. However, results differed significantly between strains and sexes. Moreover, the 10-day interval between the two tested cohorts uncovered a strong difference in the behavioral results, confirming the significant impact of maturation on behavioral patterns. Interestingly, the results of distinct behavioral experiments were directly correlated with the weight of mice, which may explain the lack of reproducibility of some behavioral results in genetically-modified mice. Our study paves the way for better reproducibility of behavioral tests by addressing the effect of the developmental stage, strain, sex, and weight of mice on achieving the face validity of neuropsychiatric disorder-associated motor dysfunctions.

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Activation of immunological network by chronic low-dose-rate irradiation in wild-type mouse strains: Analysis of immune cell populations and surface molecules

International Journal of Radiation Biology ◽

10.1080/09553000500519808 ◽

2005 ◽

Vol 81 (10) ◽

pp. 721-729 ◽

Cited By ~ 69

Author(s):

Yasuhiro Ina ◽

Kazuo Sakai

Keyword(s):

Dose Rate ◽

Low Dose ◽

Immune Cell ◽

Wild Type Mouse ◽

Mouse Strains ◽

Cell Populations ◽

Wild Type ◽

Surface Molecules ◽

Low Dose Rate

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Comparative analysis of the gut microbiota composition in the Cln1R151X and Cln2R207X mouse models of Batten disease and in three wild-type mouse strains

Archives of Microbiology ◽

10.1007/s00203-020-02007-6 ◽

2020 ◽

Author(s):

Camille Parker ◽

Jing Zhao ◽

David A. Pearce ◽

Attila D. Kovács

Keyword(s):

Comparative Analysis ◽

Gut Microbiota ◽

Mouse Models ◽

Batten Disease ◽

Wild Type Mouse ◽

Mouse Strains ◽

Microbiota Composition ◽

Wild Type ◽

Gut Microbiota Composition

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Alterations in the number of motoneurons containing immunoreactive calcitonin gene-related peptide(CGRP)& choline acetyltransferase(ChAT) in the cervical spinal cord of the wobbler mouse during the development of the motoneuron disease

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100141226 ◽

1995 ◽

Vol 53 ◽

pp. 970-971

Author(s):

L. Vacca-Galloway ◽

Y.Q. Zhang ◽

P. Bose ◽

S.H. Zhang

Keyword(s):

Spinal Cord ◽

Early Stage ◽

Cervical Spinal Cord ◽

Wild Type Mouse ◽

Reflex Response ◽

Mouse Strains ◽

Behavioral Tests ◽

Wobbler Mouse ◽

Stage 4 ◽

Stage 1

The Wobbler mouse (wr) has been studied as a model for inherited human motoneuron diseases (MNDs). Using behavioral tests for forelimb power, walking, climbing, and the “clasp-like reflex” response, the progress of the MND can be categorized into early (Stage 1, age 21 days) and late (Stage 4, age 3 months) stages. Age-and sex-matched normal phenotype littermates (NFR/wr) were used as controls (Stage 0), as well as mice from two related wild-type mouse strains: NFR/N and a C57BI/6N. Using behavioral tests, we also detected pre-symptomatic Wobblers at postnatal ages 7 and 14 days. The mice were anesthetized and perfusion-fixed for immunocytochemical (ICC) of CGRP and ChAT in the spinal cord (C3 to C5).Using computerized morphomety (Vidas, Zeiss), the numbers of IR-CGRP labelled motoneurons were significantly lower in 14 day old Wobbler specimens compared with the controls (Fig. 1). The same trend was observed at 21 days (Stage 1) and 3 months (Stage 4). The IR-CGRP-containing motoneurons in the Wobbler specimens declined progressively with age.

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Inducible Nitric Oxide Synthase Is Not Essential for Control of Trypanosoma cruzi Infection in Mice

Infection and Immunity ◽

10.1128/iai.72.7.4081-4089.2004 ◽

2004 ◽

Vol 72 (7) ◽

pp. 4081-4089 ◽

Cited By ~ 40

Author(s):

Kara L. Cummings ◽

Rick L. Tarleton

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Trypanosoma Cruzi ◽

Inducible Nitric Oxide Synthase ◽

Interleukin 1 ◽

Mouse Strains ◽

Wild Type ◽

Necrosis Factor Alpha ◽

Oxide Synthase ◽

Inducible Nitric Oxide

ABSTRACT Immune control of many intracellular pathogens, including Trypanosoma cruzi, is reported to be dependent on the production of nitric oxide. In this study, we show that mice deficient in inducible nitric oxide synthase (iNOS or NOS2) exhibit resistance to T. cruzi infection that is comparable to that of wild-type mice. This is the case for two iNOS-deficient mouse strains, Nos2tm1Lau and Nos2 N5, infected with the Brazil or Tulahuen strain of T. cruzi. In all cases, blood parasitemia, tissue parasite load, and survival rates are similar between wild-type and iNOS-deficient mice. In contrast, both wild-type and Nos2tm1Lau mice died within 32 days postinfection when treated with the nitric oxide synthase inhibitor aminoguanidine. Increased transcription of NOS1 or NOS3 is not found in iNOS-knockout (KO) mice, indicating that the absence of nitric oxide production through iNOS is not compensated for by increased production of other NOS isoforms. However, Nos2tm1Lau mice exhibit enhanced expression of tumor necrosis factor alpha, interleukin-1, and macrophage inflammatory protein 1α compared to that of wild-type mice, and these alterations may in part compensate for the lack of iNOS. These results clearly show that iNOS is not required for control of T. cruzi infection in mice.

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Different roles for Pax6 in the optic vesicle and facial epithelium mediate early morphogenesis of the murine eye

Development ◽

10.1242/dev.127.5.945 ◽

2000 ◽

Vol 127 (5) ◽

pp. 945-956 ◽

Cited By ~ 6

Author(s):

J.M. Collinson ◽

R.E. Hill ◽

J.D. West

Keyword(s):

Histological Analysis ◽

Eye Development ◽

Wild Type Mouse ◽

Lens Epithelium ◽

Optic Vesicle ◽

Wild Type ◽

Adhesive Properties ◽

Optic Vesicles ◽

Lens Placode ◽

Mutant Cells

Chimaeric mice were made by aggregating Pax6(−/−) and wild-type mouse embryos, in order to study the interaction between the optic vesicle and the prospective lens epithelium during early stages of eye development. Histological analysis of the distribution of homozygous mutant cells in the chimaeras showed that the cell-autonomous removal of Pax6(−/−) cells from the lens, shown previously at E12.5, is nearly complete by E9.5. Most mutant cells are eliminated from an area of facial epithelium wider than, but including, the developing lens placode. This result suggests a role for Pax6 in maintaining a region of the facial epithelium that has the tissue competence to undergo lens differentiation. Segregation of wild-type and Pax6(−/−) cells occurs in the optic vesicle at E9.5 and is most likely a result of different adhesive properties of wild-type and mutant cells. Also, proximo-distal specification of the optic vesicle (as assayed by the elimination of Pax6(−/−) cells distally), is disrupted in the presence of a high proportion of mutant cells. This suggests that Pax6 operates during the establishment of patterning along the proximo-distal axis of the vesicle. Examination of chimaeras with a high proportion of mutant cells showed that Pax6 is required in the optic vesicle for maintenance of contact with the overlying lens epithelium. This may explain why Pax6(−/−) optic vesicles are inefficient at inducing a lens placode. Contact is preferentially maintained when the lens epithelium is also wild-type. Together, these results demonstrate requirements for functional Pax6 in both the optic vesicle and surface epithelia in order to mediate the interactions between the two tissues during the earliest stages of eye development.

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Incomplete nucleoside transport deficiency with increased hypoxanthine transport capability in mutant T-lymphoblastoid cells

Molecular and Cellular Biology ◽

10.1128/mcb.6.4.1296-1303.1986 ◽

1986 ◽

Vol 6 (4) ◽

pp. 1296-1303

Author(s):

B Aronow ◽

P Hollingsworth ◽

J Patrick ◽

B Ullman

Keyword(s):

Binding Site ◽

Wild Type Mouse ◽

Single Step ◽

Nucleoside Transport ◽

Wild Type ◽

Surface Binding ◽

T Lymphoma Cells ◽

Residual Transport ◽

T Lymphoma ◽

Mutant Cells

From a mutagenized population of wild-type mouse (S49) T-lymphoma cells, a clone, 80-5D2, was isolated in a single step by virtue of its ability to survive in 80 nM 5-fluorouridine. Unlike previously isolated nucleoside transport-deficient cell lines (A. Cohen, B. Ullman, and D. W. Martin, Jr., J. Biol. Chem. 254:112-116, 1979), 80-5D2 cells were only slightly less sensitive to growth inhibition by a variety of cytotoxic nucleosides and were capable of proliferating in hypoxanthine-amethopterin-thymidine-containing medium. The molecular basis for the phenotype of 80-5D2 cells was incomplete deficiency in the ability of the mutant cells to translocate nucleosides across the plasma membrane. Interestingly, mutant cells were more capable than wild-type cells of transporting the nucleobase hypoxanthine. Residual transport of adenosine into 80-5D2 cells was just as sensitive to inhibition by nucleosides and more sensitive to inhibition by hypoxanthine than that in wild-type cells, indicating that the phenomena of ligand binding and translocation can be uncoupled genetically. The 80-5D2 cells lacked cell surface binding sites for the potent inhibitor of nucleoside transport p-nitrobenzylthioinosine (NBMPR) and, consequently, were largely resistant to the physiological effects of NBMPR. However, the altered transporter retained its sensitivity to dipyridamole, another inhibitor of nucleoside transport. The biochemical phenotype of the 80-5D2 cell line supports the hypothesis that the determinants that comprise the nucleoside carrier site, the hypoxanthine carrier site, the NBMPR binding site, and the dipyridamole binding site of the nucleoside transport function of mouse S49 cells are genetically distinguishable.

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The Na+/H+ exchanger isoform 3 is required for active paracellular and transcellular Ca2+ transport across murine cecum

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00490.2012 ◽

2013 ◽

Vol 305 (4) ◽

pp. G303-G313 ◽

Cited By ~ 21

Author(s):

Juraj Rievaj ◽

Wanling Pan ◽

Emmanuelle Cordat ◽

R. Todd Alexander

Keyword(s):

Water Movement ◽

Water Flux ◽

Wild Type Mouse ◽

Wild Type ◽

Rt Pcr ◽

Ussing Chambers ◽

Voltage Clamps ◽

Paracellular Absorption ◽

Mouse Intestine

Intestinal calcium (Ca2+) absorption occurs via paracellular and transcellular pathways. Although the transcellular route has been extensively studied, mechanisms mediating paracellular absorption are largely unexplored. Unlike passive diffusion, secondarily active paracellular Ca2+ uptake occurs against an electrochemical gradient with water flux providing the driving force. Water movement is dictated by concentration differences that are largely determined by Na+ fluxes. Consequently, we hypothesized that Na+ absorption mediates Ca2+ flux. NHE3 is central to intestinal Na+ absorption. NHE3 knockout mice (NHE3−/−) display impaired intestinal Na+, water, and Ca2+ absorption. However, the mechanism mediating this latter abnormality is not clear. To investigate this, we used Ussing chambers to measure net Ca2+ absorption across different segments of wild-type mouse intestine. The cecum was the only segment with net Ca2+ absorption. Quantitative RT-PCR measurements revealed cecal expression of all genes implicated in intestinal Ca2+ absorption, including NHE3. We therefore employed this segment for further studies. Inhibition of NHE3 with 100 μM 5-( N-ethyl- N-isopropyl) amiloride decreased luminal-to-serosal and increased serosal-to-luminal Ca2+ flux. NHE3−/− mice had a >60% decrease in luminal-to-serosal Ca2+ flux. Ussing chambers experiments under altered voltage clamps (−25, 0, +25 mV) showed decreased transcellular and secondarily active paracellular Ca2+ absorption in NHE3−/− mice relative to wild-type animals. Consistent with this, cecal Trpv6 expression was diminished in NHE3−/− mice. Together these results implicate NHE3 in intestinal Ca2+ absorption and support the theory that this is, at least partially, due to the role of NHE3 in Na+ and water absorption.

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Quantitating Aortic Atherosclerosis in Rabbits and Mice

Microscopy and Microanalysis ◽

10.1017/s1431927600008473 ◽

1997 ◽

Vol 3 (S2) ◽

pp. 317-318

Author(s):

David A. Sanan ◽

Dale L. Newland

Keyword(s):

Gene Knockout ◽

Laboratory Mouse ◽

Lipoprotein Metabolism ◽

Wild Type Mouse ◽

Mouse Strains ◽

Chow Diet ◽

Homologous Genes ◽

Normal Chow ◽

Metabolism Gene ◽

Knockout Technology

Build-up of visible atherosclerotic plaque in the arteries is readily quantifiable. The mouse and the rabbit provide useful models for understanding the pathogenesis of atherosclerosis by investigating the effects of genetic and dietary perturbations.Although the wild type mouse does not develop atherosclerosis, atherosclerosis susceptibility genes have been identified in some laboratory mouse strains which do. Furthermore, transgenic technology and gene targeting have produced genetically modified mice that express various apolipoproteins, enzymes and cofactors involved in human lipoprotein metabolism. Gene “knockout” technology allows transgene expression without interference from homologous genes. One notable “knockout” mouse, deficient in apolipoprotein E, develops spontaneous atherosclerosis on a normal chow diet. Transgenic modulations of the atherosclerotic responses of these highly susceptible mice are more pronounced and easily measured. Small, cheap and fast breeding, mice are convenient animal models. But to make mice susceptible to atherosclerosis, their genetic background has to be so drastically altered that the resulting lipoprotein metabolism may not model the human metabolism accurately enough.

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